1. Field of the Invention
This invention relates generally to devices and methods for noninvasive in vivo measurement of blood hematocrit and, more specifically, to devices and methods for such measurement that use impedance and pressure plethysmography.
2. Background of Related Art
The xe2x80x9chematocritxe2x80x9d of blood, which is defined as the percentage of whole blood volume occupied by erythrocytes (i.e., red blood cells), is an important measure of patient well being in cases of trauma, blood loss by disease, iron depletion in pregnancy, dietary iron deficiency, and a number of more specific medical conditions.
Hematocrit has traditionally been measured by centrifuging a column of blood, which has been extracted from the patient, in a glass tube, until the erythrocytes are compacted by centrifugal force to one end of the tube. The hematocrit is determined by measuring the length of the tube containing dark red material and dividing by the total length of the liquid column in the tube. These length observations are usually made visually, but are also made, in some cases, by automated optical means of various designs. Besides centrifugal hematocrit determinations, hematocrit is also derived and reported by various automated blood analyzers which count erythrocytes optically in unpacked blood. This erythrocyte count correlates with packed cell hematocrit and the derived hematocrit is reported.
It is noted that the above-described methods for obtaining hematocrit are invasive, that is they require that blood be removed from the patient in order to determine the hematocrit. A non-invasive method would be desirable because it would subject the patient to less pain and inconvenience and would preserve the patient""s blood for its normal functions.
It has long been recognized by biomedical researchers that the electrical impedance of blood varies with hematocrit and that, as a result of this relationship, it should be possible to derive hematocrit from the measurement of blood impedance. Hematocrit has been successfully determined by measuring the impedance of blood that has been extracted from the patient and placed in an impedance measuring cell of controlled dimensions, where a fixed volume of the blood is contained, maintained at a known temperature, and agitated to maintain uniform cell distribution. Examples of such successful measurements are given by Okada and Schwan in xe2x80x9cAn Electrical Method to Determine Hematocrits,xe2x80x9d IRE Transactions in Medical Electronics, ME-7:188-192 (1960) and by deVries et al. in xe2x80x9cImplications of the Dielectrical Behavior of Human Blood for Continuous Online Measurement of Hematocrit,xe2x80x9d Medical and Biological Engineering and Computing, pages 445-448 (1993) (hereinafter xe2x80x9cdeVriesxe2x80x9d). Like the centrifugal methods, these methods are invasive, however, and thus do not satisfy the need for a non-invasive hematocrit measurement. The impedance methods have, however, provided the inspiration for some ingenious inventions to measure hematocrit in-vivo and non-invasively.
The first in-vivo impedance measurement of hematocrit known to the inventors was reported by Yamakoshi et al. in xe2x80x9cNoninvasive Measurement of Hematocrit by Electrical Admittance Plethysmography Technique,xe2x80x9d IEEE Transactions, BMB-27, 3:156-161(1980). This measurement was made by immersing the finger of the test subject in a saline solution contained in a chamber fitted with impedance measuring electrodes. The electrolyte concentration of the saline solution was then varied by mixing in either water or more concentrated saline until the pulsatile variations of impedance caused by the increased volume of blood on each pulse were minimized. When this minimization of pulses occurred, the saline solution had the same resistivity as the blood in the pulsing arteries and this resistivity could be correlated against the known, previously determined relationship between resistivity and hematocrit.
U.S. Pat. No. 5,526,808 (hereinafter xe2x80x9cthe ""808 Patentxe2x80x9d), issued to Kaminsky and assigned to Microcor, Inc., the assignee of the present invention, describes another impedance method for measuring hematocrit noninvasively and in vivo. This method draws upon the observation that hematocrit determines the frequency vs. impedance profile of blood. In addition, the method of the ""808 Patent uses the pulsatile change of impedance in a finger or other limb of the body that occurs when each heartbeat pushes new blood into the organ where the measurement is made to separate the non-blood tissue impedance from the blood impedance.
The mathematical model upon which this method is based relies upon the assumption that, as blood pulses into a finger or other body part where the hematocrit measurement is being made, the admittance (i.e., the reciprocal of impedance) change that occurs is due to the increased volume of blood providing a new current path in parallel with the old current path present before the pulse occurs. Thus, the difference in admittance between baseline, when no new blood is in the limb, and during the pulse, when new arterial blood has entered the limb, is due to the new blood. The numerical value of this admittance difference is proportional to the volume of the new blood times the admittance of the new blood.
As shown in deVries, the admittance vs. frequency characteristics of blood have a characteristic shape that depends upon hematocrit. Comparing the shapes of either the magnitude or the phase versus the frequency of the admittance, derived for the pulsed blood, against known characteristic hematocrit-dependent shapes gives a measure of hematocrit. The known characteristic shapes can be derived from a database obtained from patients having hematocrits independently measured by the centrifugal method previously described.
U.S. Pat. No. 5,642,734 (hereinafter xe2x80x9cthe ""734 Patentxe2x80x9d), issued to Ruben et al. and assigned to Microcor, Inc., the assignee of the present invention, describes some additional methods to obtain in vivo hematocrit results. First, the ""734 Patent describes using pressurized cuffs, in various ways, to change the amount of blood in the organ (e.g., the finger) at which hematocrit is noninvasively measured. Second, the ""734 Patent describes a unique electronic system for driving electrodes attached to the body part under measurement and for deriving phase, as well as amplitude information from impedance measurements of the body part. Third, the ""734 Patent teaches the use of a neural network computer algorithm to relate measured impedance and other data to hematocrit based upon matching a database obtained from a number of prior measurements of patients with separately-determined hematocrits.
In the field of blood oxygen saturation measurement, as opposed to the field of blood hematocrit measurement that has been under discussion thus far, U.S. Pat. No. 5,111,817 (hereinafter xe2x80x9cthe ""817 Patentxe2x80x9d), issued to Clark et al., observes that the accurate measurement of blood oxygen saturation levels in arteries (SaO2) in a body part under measurement, such as a finger, is typically hindered by different blood oxygen saturation levels in capillaries (ScO2) in the body part. The ""817 Patent teaches a method for correcting measurements of SaO2 for the effects of ScO2. In this method, a pressure cuff applies a pressure to the body part under measurement that is equal to the mean arterial blood pressure in the body part. As a result, measurements from the body part are dominated by the effects of the actual SaO2 in the body part, so that the measured SaO2 is closer to actual SaO2.
While the use of pressure cuffs are known in the art to assist in the noninvasive measurement of hematocrit and blood oxygen saturation, as is the use of electrode pairs to noninvasively measure hematocrit, the art does not teach specific configurations of apparatus that are used in the noninvasive measurement of hematocrit.
The present invention includes apparatus configured for use in the noninvasive measurement of the hematocrit of a patient. Apparatus incorporating teachings of the present invention include two or more pairs of electrodes. A pressurization component may also be associated with the apparatus of the present invention.
A first embodiment of electrodes incorporating teachings of the present invention includes four individual electrodes that are paired in inner and outer sets. The electrodes may be substantially L-shaped. A first member of each electrode is configured to contact and to be at least partially wrapped around a body part at which hematocrit is to be noninvasively measured. A second member of each electrode is configured to communicate with external electrical componentry that will either apply a voltage to the body part or measure impedance at the body part, as will be described hereinafter in greater detail. In a variation of the first embodiment, one or more of the electrodes may be substantially linear, with a first end thereof configured to be at least partially wrapped around a body part and a second end thereof configured to be connected to external electronic componentry.
A second embodiment of electrodes useful in apparatus of the present invention has two elements, each including a pliable substrate and two electrodes, an electrode of an outer set and an electrode of an inner set. The pliable substrate preferably conforms to the shape of the body part at which hematocrit is to be noninvasively measured and may include a substantially planar member or be configured to at least partially receive the body part (e.g., an open- or close-ended tube configured to at least partially receive a finger). Again, the electrodes may be substantially L-shaped and include a first member and a second member. At least a portion of the first member of each electrode is secured to and carried by the pliable substrate. Thus, as the first members of each of the L-shaped electrodes are brought into contact with a body part at which hematocrit is to be noninvasively measured and the pliable substrate of each of the two elements is at least partially wrapped around the body part, the first member of each electrode is also at least partially wrapped around the body part. In a variation of the second embodiment, one or more of the electrodes may be substantially linear, with a first end thereof configured to be at least partially wrapped around a body part and a second end thereof configured to be connected to external electronic componentry.
A third embodiment of electrodes includes a single, pliable substrate that at least partially carries four electrodes arranged relative to the substrate in inner and outer sets. The pliable substrate preferably conforms to the shape of the body part at which hematocrit is to be noninvasively measured and may include a substantially planar member or be configured to at least partially receive the body part (e.g., as an open-ended or close-ended tube configured to at least partially receive a finger). The electrodes may be L-shaped, as described previously herein with respect to the first and second electrode embodiments, or substantially linear, and are configured to communicate with external electronic componentry.
Apparatus incorporating teachings of the present invention also include a pressurization component configured to apply a predetermined amount of pressure to the body part at which hematocrit is to be noninvasively measured.
A first embodiment of the pressurization component includes a pliable bladder configured to be at least partially wrapped around the body part, over the inner and outer pairs of electrodes, so as to apply increased pressure to the body part as pressure within the bladder is increased (e.g., with air or another fluid).
In a second embodiment, a pliable substrate upon which portions of the electrodes are carried, as in the second and third electrode embodiments described previously herein, comprises a pliable bladder. Accordingly, at least a portion of at least one electrode of each of the inner and outer electrode pairs may be secured to or otherwise carried by the pliable bladder. Prior to introducing pressure into the pliable bladder, the bladder may be substantially planar or configured to at least partially receive the body part at which hematocrit is to be noninvasively measured (e.g., as an open-ended or close-ended tube configured to at least partially receive a finger).
These pliable bladder embodiments of the pressurization component are configured to be connected to a source of pressure. As the pliable bladder is pressurized (e.g., by air pressure or pressure of another fluid), pressure is applied to at least a portion of the body part.
In addition, these pliable bladders may line a receptacle formed in a rigid member and configured to at least partially receive the body part.
In a third embodiment of pressurization component incorporating teachings of the present invention, inner and outer pairs of electrodes, such as those of the first, second, and third electrode embodiments described previously herein, are placed in contact with and at least partially wrapped around a body part at which hematocrit will be measured. The body part is at least partially inserted into a pressure chamber, which is in fluid communication with a source of positive pressure. Portions of one or both electrodes of the inner and outer pairs of electrodes in contact with the body part may also be inserted into the pressure chamber. As the body part is positioned within the pressure chamber, an at least partial seal is formed around the body part. Accordingly, as a positive pressure forms within the pressure chamber, pressure will be applied to the body part.
A system for noninvasively measuring the hematocrit of blood perfusing a living body part (e.g., a finger) in accordance with teachings of the present invention includes a non-invasive hematocrit measurement apparatus and external electronic componentry associated therewith. The electronic componentry of the system includes circuitry that drives first and second alternating currents of different frequencies (e.g., 100 KHz and 10 MHz) between separate points on the body part. The alternating currents may be applied to the body part through input electrodes attached to the body part at the separate points. Also, additional circuitry monitors first and second signals (e.g., voltage waveforms) induced in the body part by the first and second currents (e.g., by monitoring output electrodes attached to the body part), and other circuitry generates first and second pulsatile signals and first and second baseline signals from the first and second induced signals. Determining circuitry then calculates the hematocrit of the blood from the first and second pulsatile signals and the first and second baseline signals. This calculation may be performed, for example, by determining the hematocrit (H) from the following equation:
[(1+(fxe2x88x921)H)/(1xe2x88x92H)]{1+[((af(exe2x88x92bxxe2x88x92c))x/(1xe2x88x92x))xe2x88x921]H}/{1+[((af(exe2x88x92bxxe2x88x92c))/(1xe2x88x92x))xe2x88x921]H}=Cxc2x7(xcex94VoltH/VH2)/(xcex94VoltL/VoltL2),
where (f, a, b, x, c, and C) are various constants, as will be described below, xcex94VoltH and xcex94VoltL are the first and second pulsatile signals, and VH and VL are the first and second baseline signals.
In accordance with another embodiment of the system of the present invention, a system for measuring the hematocrit of blood perfusing a living body part includes electrodes positioned on the surface of the body part. A measuring device measures the electrical impedance at one or more frequencies between the electrodes. Also, a chamber is positioned to surround the body part between the electrodes, and a measuring apparatus measures pulsatile blood volume by the pulsatile-related change in internal pressure within the chamber. Further, a calculating device (e.g., a programmed microprocessor) determines the blood hematocrit from the measurements of impedance and pulsatile blood volume. The device may determine the hematocrit H in accordance with the following equations:
H=(xcfx81xe2x88x9258)/(0.01 xcfx81+0.435), and
xcfx81=xcex94VZ02/L2xcex94Z,
where xcex94V is the change in pulsatile blood volume at any point in time, xcex94Z is the change of impedance at the same point in time, L is a constant which will be described below, and Z0 is the baseline impedance at the beginning of each pulse.
In a further embodiment, the system for determining blood hematocrit includes circuitry that produces a current signal including a first, relatively low frequency portion and a second, relatively high frequency portion, and the hematocrit measuring apparatus, which stimulates a living body part containing blood with the current signal. Also, additional circuitry of the hematocrit measuring apparatus is used to sense voltages at the first and second frequencies induced in the body part by the stimulation thereof, and further circuitry detects signal envelopes of the sensed voltages, with each signal envelope having a pulsatile component and a baseline component. Isolation circuitry isolates the pulsatile components and baseline components of the detected signal envelopes, and extraction circuitry extracts one or more sets of time-matched segments of the isolated pulsatile components and one or more sets of time-matched segments of the isolated baseline components. Further, other circuitry effectively correlates the blood hematocrit to the product of the ratio of the time-matched segments of the pulsatile components and the inverse ratio of the squares of the time-matched segments of the baseline components.
Another embodiment of the system includes an apparatus for determining the hematocrit of blood perfusing a living body part from relatively low frequency pulsatile and baseline signals induced in the body part, and from relatively high frequency pulsatile and baseline signals also induced in the body part, includes circuitry that effectively determines the ratio of the product of the relatively high frequency pulsatile signal and the square of the relatively low frequency baseline signal to the product of the relatively low frequency pulsatile signal and the square of the relatively high frequency baseline signal. The apparatus also includes circuitry that correlates the blood hematocrit to the effectively determined ratio.
Other embodiments of the invention include methods of measuring the hematocrit of blood perfusing a living body part, and a method of determining blood hematocrit, that generally correspond to the systems and apparatus described above.
Other features and advantages of the present invention will become apparent to those of skill in the art through a consideration of the ensuing description, the accompanying drawings, and the appended claims.